Single-cell transcriptome and TCR profiling reveal activated and expanded T cell populations in Parkinson's disease

Given the chronic inflammatory nature of Parkinson's disease (PD), T cell immunity may be important for disease onset. Here, we performed single-cell transcriptome and TCR sequencing, and conducted integrative analyses to decode composition, function and lineage relationship of T cells in the blood and cerebrospinal fluid of PD. Combined expression and TCR-based lineage tracking, we discovered a large population of CD8⁺ T cells showing continuous progression from central memory to terminal effector T cells in PD patients. Additionally, we identified a group of cytotoxic CD4⁺ T cells (CD4 CTLs) remarkably expanded in PD patients, which derived from Th1 cells by TCR-based fate decision. Finally, we screened putative TCR-antigen pairs that existed in both blood and cerebrospinal fluid of PD patients to provide potential evidence for peripheral T cells to participate in neuronal degeneration. Our study provides valuable insights and rich resources for understanding the adaptive immune response in PD.